Frank first described "premenstrual tension syndrome" (PMS) nearly 60 years ago (Frank, R. T. 1931, Arch. Neurol. Psychiatr. 26: 1053-1057).
Since then, PMS has been characterized by a number of both physical and psychological symptoms. It has recently been labeled a significant medical condition (Seikus, P., 1988, Better Nutrition 50(2): 14-15). PMS is defined as a psychoneuro-endocrine disorder encompassing a wide variety of symptoms. These symptoms regularly occur during the luteal phase of the menstrual cycle and usually abate after the menstrual flow begins. Symptoms can range from mild to incapacitating in severity. It has been estimated that as many as 20 to 50 percent of all regularly menstruating women experience moderate to severe PMS symptoms during their reproductive years. (Reid, R. L., et al., 1981, Am. J. Obstet. Gynecol. 139(1): 86). Some studies report that 100 percent of women experience some mild symptoms during this period.
The common symptoms of PMS include breast swelling and tenderness, tension, anxiety, emotional lability, irritability, fatigue, abdominal bloating and cramps, headache, backache, edema of the hands, ankles and face, nausea and vomiting, difficulty in sleeping, increased thirst or appetite and craving for high-carbohydrate foods, increased or decreased libido, and acneiform eruptions. Women with severe PMS have been shown to possess higher levels of neurotic behavior and trait anxiety than those with less severe symptoms. (Price, W. A., et al., 1985, Resident and Staff Physician 31(5): 35.
Numerous hypotheses have been advanced to explain the pathophysiology of PMS. The hypotheses include hormonal imbalances, hormonal deficiencies, vitamin deficiencies, hypoglycemia, endogenous hormone allergy, psychosomatic dysfunction, fluid retention and withdrawal imbalance, and alteration of endogenous opiates.
In 1931, Frank attributed the signs and symptoms of PMS to excess estrogen. Data to support Frank's hypothesis of an excessive estrogen effect have been inconclusive and contradictory. Subsequently, Israel (1938, JAMA 110: 721) suggested that a deficiency of progesterone leading to an unopposed estrogenic effect was responsible for PMS. Evidence that it was progesterone withdrawal as opposed to progesterone deficiency led workers in the 1950's to propose the administration of progesterone or testosterone to combat the effects of PMS. Progestin treatment remains popular today although its efficacy has never been demonstrated satisfactorily.
The use of vitamin B.sub.6 therapy was first advocated in the 1940's. Vitamin B.sub.6 has been shown (1) to correct deficient estrogen metabolism, and (2) to play a role in the regulation of the synthesis of dopamine and serotonin within the brain. However, following a study in which Zondek and Brezezinski (1948, Br. J. Obstet. Gynaecol. 55: 273) demonstrated normal estrogen levels in women with severe vitamin B deficiency, and numerous studies which failed to demonstrate a significant and consistent dopaminergic effect of vitamin B.sub.6, this explanation for PMS has lost popularity.
Vitamin A was for a time implicated in the etiology of PMS. Hypothesizing that vitamin A might play a role in correcting aberrant estrogen metabolism, Argonz and Abinzano (1950, J. Clin. Endocrinol. Metab. 10: 1579) successfully treated 30 PMS patients with large doses of vitamin A. Vitamin A was thought to reduce PMS symptoms through opposition to thyroid hyperfunction or by exerting a direct antiestrogenic or diuretic effect.
The role of vitamin therapy in PMS awaits further clarification, but it is now thought that the existence of a cyclic vitamin deficiency in PMS patients is unlikely. While some researchers have continued to explore the role of vitamins, including vitamin E (London, R. S., et al., 1983, J. Am. Coll. Nutr. 2:115-22), other workers have even called for caution in the use of vitamin B.sub.6 as a treatment for PMS (Kendall, K. E., et al., 1987, Obstet. and Gynecol. 70(2): 145-149).
Increased carbohydrate tolerance in the premenstruum has been said to account for the craving for sweets evidenced in some PMS patients. Reactive hypoglycemia, also once thought to be linked to the cause of PMS symptoms, cannot be linked to the cause of PMS symptoms other than the occasional craving for sweets seen in some women. Certain evidence suggests that when it does occur reactive hypoglycemia is usually asymptomatic and has been observed in subjects who show no signs of PMS as well as those demonstrating classical symptoms of PMS (Reid, R. L., et al., 1981, Am. J. Obstet. Gynecol. 139(1): 88).
Endogenous hormone allergy has also been said to play a role in PMS. However, this theory remains suspect given the unreliable nature of skin testing procedures employed in past studies.
Psychosomatic disorders or psychic factors are now widely believed to follow physiological, biochemical or anatomical changes resulting from hormonal effects. Still, psychotherapy and/or the use of a variety of tranquilizing agents have in the past been found to be only somewhat effective in treating PMS.
In 1941, Greenhill and Fried (1941, JAMA, 117: 504) proposed that sodium retention induced by ovarian steroids was the lone factor responsible for all of the symptom of PMS. They believed that Frank's success in treating PMS using cathartics was based upon their acting to eliminate excess estrogen through their dehydrating effect. Since then, diuretics have been alleged to be an effective treatment for PMS. No study, to date, has appropriately shown the improvement of PMS symptomatology using diuretics.
Current research has implicated a number of neurotransmitters and hormones as markers or etiologic agents. One promising area of research involves the endorphins-endogenous opioid peptides. Several prominent symptoms of PMS, e.g. nervousness, restlessness, cramps, nausea and vomiting are similar to the symptoms of opiate withdrawal. This similarity has led workers to hypothesize that beta-endorphin withdrawal or imbalance may be responsible for many of the PMS symptoms. This hypothesis is further supported by one study which showed that the administration of naloxone, an opiate antagonist, was less effective in treating PMS than placebo. Furthermore, the withdrawal of endorphins, which is known to vary with estrogen levels, has been shown to be positively correlated with PMS.
Reid and Yen (1981, Am. J. Obstet. Gynecol., 139(1): 96) postulated an aberrant release of or sensitivity to alpha-MSH and beta-endorphins during the luteal phase of the menstrual cycle as triggering a number of neuroendocrine changes responsible for PMS.
Other recent evidence has been advanced to suggest that PMS is related to neuroendocrine function. Muse et al. (1984, N. Engl. J. Med. 311: 1345-1349) in 1984 reported the effective and beneficial treatment of medical ovariectomy-reversible ovarian failure induced by a gonadotrophin releasing hormone agonist. In a crossover study, 8 patients were relieved by daily administration of a gonadotrophin releasing hormone agonist. Although the use of gonadotrophin releasing hormone agonists seemed to have a physiologic effect on the symptoms of PMS, the clinical practicality of this treatment for individuals with less than disabling symptoms of PMS is questionable because of undesirable consequences such as osteoporosis.
Today physicians are faced with an array of therapeutic modalities ranging from diuretics, to vitamins, to hormonal suppositories. The most popular approaches have involved vitamin B.sub.6 and progesterone supplementation. Yet, double-blind, placebo-controlled trials have not substantiated the benefit or effectiveness of any one treatment.
Premenstrual syndrome, as noted above, encompasses a broad spectrum of symptomatology that is probably related to a vascular and smooth muscle responsiveness or to hormonal secretion. Premenstrual headache might be explained as a primary vasospastic event; abdominal cramps possibly as smooth muscle hyperexcitability. Calcium has been shown to have a role in the release of neurotransmitters, endocrine and exocrine products, in the contraction of skeletal and smooth muscle, and metabolism. Calcium's importance has been shown at the biochemical level, but its clinical application as a supplement or therapeutic modality other than for the known entities such as tetany/hypocalcemia has never been shown. Supplemental calcium's use in vascular headache, abdominal menstrual cramps, and PMS has never been studied. The precise role of calcium in the pathophysiology of PMS is not known, and whether the interaction of calcium is with ovarian linked hormones or with neuroendocrine modulators is unclear. As menstruation is related to ovarian and pituitary secretory function, it is not unreasonable to postulate a calcium-linked hormonal effect on those behavioral and somatic changes that occur during this period. Calcium coupled with these hormones may modulate the intrinsic feedback mechanisms that translate physiologic neuroendocrine and hormonal messages into behavioral and somatic changes.